We propose to investigate the nature and genetic control of immune responses to rota virus infected cells in patients with inflammatory bowel disease (IBD) and their relatives. Immune responses in vitro will be assessed using lymphocytotoxicity tests and lymphocyte transformation by rota-virus-membrane preparations. Effector lymphocytes will be obtained from peripheral blood and intestine. Target cells will include both rota-virus infected and non-infected intestinal fibroblasts. The relevant lymphocyte subpopulation will be identified and the possibility that cytotoxicity reactions are restricted by the histocompatibility antigens of the effector and target cells will be investigated. The genetics of disease susceptibility will also be studied. Our population of IBD patients will be typed both for serologically-defined and lymphocyte-defined histocompatibility antigens. Correlations will be made between markers of disease susceptibility and the segregation of the major histocompatibility complex in information IBD families. The interrelationships between viral, immunological, and genetic factors in IBD will be analyzed.